Re-irradiation (R-I) has been contemplated as a significant concern in the last few years. Indeed, Because of improvement the patient’s life expectancy and quality of life increased the necessity of performing new irradiations. Furthermore, recent machines and techniques enhanced the ability of radiation oncologists to respond positively to such requirements of R-I. However, the technical improvements face some issues linked to the tolerance of the healthy critical organs (HCOs) in proximity to the tumor requiring re-irradiation. Dose constraints for the HCOs were mainly specified for the first irradiation by delivering the total prescribed dose at a conventional dose per fraction (1.8-2 Gy), or more recently with ablative radiotherapy. These dose limits have never been truly demonstrated prospectively. At the same time, dose constraints in the context of R-I have been even less proven, and guidelines are limited and scarce. Consequently, physicians have to follow with prudence, either bits of advice or published proposals which are often based on retrospective experiments done by a few teams.
Several difficulties accompany the description of dose constraints for HCOs at the time of re-irradiation.
- upon the primary irradiation, the dose distribution in the HCOs is often inhomogeneous. Consequently, to limit the risk of proposing incomprehensible calculations, the remaining dose to deliver, is often based on the highest dose received by the HCOs during the first irradiation, occulting the part of the HCOs volume receiving the lowest doses.
- difficulty is the variation of fractionation used for R-I, even though the dose upon the first irradiation had been delivered using conventional fractionation. However, this issue could be addressed in the future due to the development and frequent use of hypofractionated treatments in radiation oncology. In addition, to overcome the use of different fractionation methods, the EQD2 or BED calculations use the alpha/beta ratio and aim to generate comparable doses independently of the dose fractionation. However, the alpha/beta ratios of most HCOs and their corresponding tissues are not well described. Furthermore, the ratio of both early and late radiation effects should be calculated for each organ, taking into consideration slowly proliferating cells versus rapidly proliferating ones.
- calculation of EQD2 and BED has been generated based on the LQ model and the dose per fraction in order to convert a classically limited total dose of 10 Gy, even though some authors argue that this model was valid up to 15 Gy per fraction.
- some authors claimed the ability of normal tissues to recover dose naivety, however, this proposition remains difficult to demonstrate and increases the risk of delivering an overdose to HCOs.
Based on the above, several steps should be considered before determining the dose that could be delivered in a second irradiation.
- Matching and comparing the first and newly acquired medical images is highly required. In addition, the HCO volumes and the dose distribution throughout these volumes must be reported.
- determine the theoretical maximum dose constraints for HCOs according to published guidelines and to express these in EQD2 or BED (D0).
- the dose distribution of the first irradiation has to be recalculated with EQD2 or BED formula. Also, the dose distribution, or simply the maximum dose, delivered upon the first irradiation to each HCO has to be recalculated with EQD2 or BED formula (D1).
- calculate the authorized dose limits for the new irradiation, the remaining dose, or the remaining dose distribution (D2), based on the following formula: D2=D0-D1.
- the D2 expressed in BED or EQD2 must be recalculated according to the prescribed fractionation for the R-I, or must be compared to the maximum dose recommended for each HCO calculated in BED or EQD2 of the newly fractionated treatment.
Three points deserve to be also discussed:
- D1 does not take into account the probable repair process which could result in increasing the remaining dose.
- the maximum recommended dose in HCOs does not take into consideration several risk factors which could influence the dose tolerance in these HCOs;
- Planning of fields should take into account the different types of organs; serial and parallel HCOs.
Regardless of all advice, some authors have published work using higher doses than those calculated in dose constraints for the first irradiation (D0). Such doses might be employed but with great caution since they are obtained once again from retrospective studies, where visible and invisible biases could have interfered with and falsified the obtained results.
Data collection is very essential to improve the oncologic response to irradiation and most importantly to enhance treatment tolerance. Networks and artificial intelligence tools could be used to help achieve these goals, and we might as well develop those at warp speed.